2666 - Impact of Upfront vs. Salvage Radiation in Low Grade Glioma

Purpose/Objective(s): The decision to observe or offer adjuvant radiation (RT) and/or systemic treatment after surgical resection for low grade gliomas (LGGs) is evolving. With increasing systemic therapy options such as isocitrate dehydrogenase inhibitors and continued concerns of RT adverse effects, there is an increasing trend to delay adjuvant RT. Here, we examine the impact of upfront versus salvage RT on target volumes and organs at risk (OAR). We hypothesized that target volumes and target overlap with the hippocampus will be decreased, while more normal brain will be spared in the upfront compared to salvage RT setting.

Materials/Methods: We performed a retrospective analysis of patients diagnosed with WHO grade 2 gliomas at a single institution from 1/1/1998-7/1/2024. Comparison of categorical and continuous variables were performed using Chi-square/Fischer exact tests or paired t-test/Wilcoxon signed rank tests respectively. Survival analysis for overall survival (OS) and progression free survival (PFS) were performed using Kaplan-Meier method and log rank test. OS and PFS were assessed from time of pathological diagnosis to event or last clinical follow up. For patients who received salvage radiation, we fused initial diagnostic post-operative brain MRIs to CT simulation scans and contoured gross tumor volume (GTV), planning target volume (PTV), and OAR volumes.

Results: 85 patients were included with a median age at time of diagnosis of 36 (range 7-69). The majority were females (61.2%) with most common subtypes of astrocytoma (60%) and oligodendroglioma (23.5%). 55.3% underwent a subtotal resection, and 35.3% of patients had a gross total resection. 40% received upfront RT, 60% received upfront adjuvant systemic therapy alone or were observed. Upfront RT was associated with improved PFS (median 207.6 months vs 46.2 months, p<0.0001) though there was no OS benefit (median not reached vs 287.8 months, p=0.7467) when compared to patients who received upfront systemic therapy or observation alone. 15 patients received salvage RT at first progression, assessment of theoretical upfront RT volumes in the salvage RT patients showed decreased PTV (30.1% reduction), increased sparing of uninvolved brain (8.9% increase in Brain-PTV), and decreased overlap between PTV and hippocampus (27.3% reduction) compared to the actual salvage RT plan, which were all statistically significant.

Conclusion: Our results show that early upfront RT in patients with LGG is associated with improved PFS. While upfront RT does not appear to have an OS benefit compared to salvage RT, we show that upfront RT may allow for decreased target volumes with less overlap between critical structures such as the hippocampus and less normal brain radiated; which in turn, may have implications for neurocognitive toxicities associated with RT.